Human monoclonal antibodies are creating a new generation of pharmaceutical agents. They can now be produced at low cost and high volume in transgenic plants as "Plantibodies". Currently, EPIcyte is using transgenic corn to produce human plantibodies against sperm and HSV2 for protective reproductive health products. The aim of this proposal is to develop an anti-HIV plantibody to help prevent HIV transmission. Specific aim 1 is to generate primary plant transformants that express a potent, broad-spectrum human anti-HIV IgG plantibody based on human monoclonal IgGb12. This human monoclonal is one of the most potent, and broad-spectrum antibodies produced to date. Specific aim 2 is to perform initial evaluation of this plantibody for HIV neutralization in vitro. In a subsequent project, this anti-HIV plantibody may then be evaluated for its efficacy for blocking transmission in several applications: (a) blocking sexual transmission (vaginal, penile, rectal, oral); (b) preventing maternal-fetal transmission; (c) preventing transmission by breast milk; (d) post-exposure prophylaxis (e.g., after coerced sex or a needle stick). PROPOSED COMMERCIAL APPLICATION: Antibody-based technology is now coming to fruition for systemic therapeutics, but one untapped commercial application for antibodies is in the prevention of infection. Blocking vertical and sexual transmission are two important applications, but the technology is so flexible that it is readily extended to the prevention of many infectious diseases.